X-ray imaging is a well known and extremely valuable tool for the early detection and diagnosis of various disease states in the human body. The use of contrast agents for image enhancement in medical x-ray imaging procedures is widespread. An excellent background on iodinated and other contrast agents for medical imaging is provided by D. P. Swanson et al, Pharmaceuticals in Medical Imaging, 1990, MacMillan Publishing Company.
The following references describe various iodine containing compounds useful in preparing x-ray contrast compositions.
U.S. Pat. No. 3,097,228 describes derivatives of 2,4,6-triiodobenzoyloxyalkanoic acids having the structure ##STR4## wherein R.sup.1 is H or lower alkyl; R.sup.2 is H or lower-alkanoyl; and R.sup.3 is H or lower alkanoylamino and R.sup.4 is lower alkyl. However, there is no suggestion of benzoyl acetals or ketals.
U.S. Pat. No. 3,144,479 describes iodinated benzoic acid esters having the formula ##STR5## wherein X is an iodine atom or an amino group and R is selected from H, alkyl, alkoxyalkyl, i.e., --CH.sub.2 --.sub.m --O--R", wherein R" is alkyl and m is 1 or 2, phenyl and a particular iodinated aromatic group. However, there is no suggestion of benzoyl acetals or ketals.
U.S. Pat. No. 4,567,034 discloses esters of diatrizoic acid as x-ray contrast agents having the structure ##STR6## However, these agents, upon hydrolysis, can release formaldehyde which is undesirable.
PCT/EP90/00053 describes iodine containing carbonate esters having the structure ##STR7## wherein R.sup.1 and R.sup.3 are an aliphatic, araliphatic, aryl or heterocyclic group; and R.sup.2 is H, aliphatic, aryl, or araliphatic for use as particulate x-ray contrast agents.
EP-A 498,482 describes nanoparticulate x-ray contrast compositions which have proven to be extremely useful in medical imaging. However, contrast agents comprised of iodinated esters, such as WIN 8883, i.e., the ethyl ester of diatrizoic acid, in some in vivo applications and for reasons that are not completely understood can exhibit less than fully satisfactory hydrolysis and/or metabolic profiles.
It would be desirable to provide compounds for use as x-ray contrast agents having improved hydrolysis and/or metabolic profiles.